Increased proportions of invasive pneumococcal disease cases amongs adults experiencing homelessness sets stage for new serotype 4 capsular-switch recombinant.

BACKGROUND: The Centers for Disease Control and Prevention's Active Bacterial Core surveillance (ABCs) identified increased serotype 4 invasive pneumococcal disease (IPD), particularly among adults experiencing homelessness (AEH). METHODS: We quantified IPD cases during 2016-2022. Employing genomic-based characterization of IPD isolates, we identified serotype-switch variants. Recombinational analyses were used to identify the genetic donor and recipient strains that generated a serotype 4 progeny strain. We performed phylogenetic analyses of the serotype 4 progeny and serotype 12F genetic recipient to determine genetic distances. RESULTS: We identified 30 inter-related (0-21 nucleotide differences) IPD isolates recovered during 2022-2023, corresponding to a serotype 4 capsular-switch variant. This strain arose through a multi-fragment recombination event between serotype 4/ST10172 and serotype 12F/ST220 parental strains. Twenty-five of the 30 cases occurred within Oregon. Of 29 cases with known residence status, 16 occurred in AEH. Variant emergence coincided with a 2.6-fold increase (57 to 148) of cases caused by the serotype 4/ST10172 donor lineage in 2022 compared to 2019 and its first appearance in Oregon. Most serotypes showed sequential increases of AEH IPD/all IPD ratios during 2016-2022 (for all serotypes combined, 247/2198, 11.2% during 2022 compared to 405/5317, 7.6% for 2018-2019, p<0.001). Serotypes 4 and 12F each caused more IPD than any other serotypes in AEH during 2020-2022 (207 combined reported cases primarily in 4 western states accounting for 38% of IPD in AEH). CONCLUSION: Expansion and increased transmission of serotypes 4 and 12F among adults potentially led to recent genesis of an impactful hybrid "serotype-switch" variant.

Positive Correlation Between Candida auris Skin-Colonization Burden and Environmental Contamination at a Ventilator-Capable Skilled Nursing Facility in Chicago.

BACKGROUND: Candida auris is an emerging multidrug-resistant yeast that contaminates healthcare environments causing healthcare-associated outbreaks. The mechanisms facilitating contamination are not established. METHODS: C. auris was quantified in residents' bilateral axillary/inguinal composite skin swabs and environmental samples during a point-prevalence survey at a ventilator-capable skilled-nursing facility (vSNF A) with documented high colonization prevalence. Environmental samples were collected from all doorknobs, windowsills and handrails of each bed in 12 rooms. C. auris concentrations were measured using culture and C. auris-specific quantitative polymerase chain reaction (qPCR) The relationship between C. auris concentrations in residents' swabs and associated environmental samples were evaluated using Kendall's tau-b (τ b) correlation coefficient. RESULTS: C. auris was detected in 70/100 tested environmental samples and 31/57 tested resident skin swabs. The mean C. auris concentration in skin swabs was 1.22 × 105 cells/mL by culture and 1.08 × 106 cells/mL by qPCR. C. auris was detected on all handrails of beds occupied by colonized residents, as well as 10/24 doorknobs and 9/12 windowsills. A positive correlation was identified between the concentrations of C. auris in skin swabs and associated handrail samples based on culture (τ b = 0.54, P = .0004) and qPCR (τ b = 0.66, P = 3.83e-6). Two uncolonized residents resided in beds contaminated with C. auris. CONCLUSIONS: Colonized residents can have high C. auris burdens on their skin, which was positively related with contamination of their surrounding healthcare environment. These findings underscore the importance of hand hygiene, transmission-based precautions, and particularly environmental disinfection in preventing spread in healthcare facilities.

Antifungal activity of nikkomycin Z against Candida auris.

BACKGROUND: Nikkomycin Z is a competitive inhibitor of chitin synthase-an enzyme needed for synthesis of the fungal cell wall. Nikkomycin Z shows promise as a treatment for coccidioidomycoses and mixed activity has been described against other fungi and yeast. To our knowledge, it has not previously been tested against the emerging fungal pathogen Candida auris. OBJECTIVES: To determine the in vitro activity of nikkomycin Z against C. auris. METHODS: Nikkomycin Z was tested by broth microdilution against a panel of 100 isolates of genetically diverse C. auris from around the world. RESULTS: Nikkomycin Z showed mixed activity against the tested isolates, with an MIC range of 0.125 to >64 mg/L. The MIC50 and MIC90 were 2 and 32 mg/L, respectively. CONCLUSIONS: These findings suggest nikkomycin Z has in vitro activity against some, but not all isolates of C. auris.

Phenotypic switching in newly emerged multidrug-resistant pathogen Candida auris.

Candida auris is an emerging, multidrug-resistant yeast that can spread rapidly in healthcare settings. Phenotypic switching has been observed in other Candida species and can potentially interfere with correct identification. The aim of this study is to address misidentification of C. auris by describing alternate phenotypes after broth enrichment and subculturing on CHROMagar Candida. Each isolate displayed different frequencies of phenotypic switching, suggesting a strain to strain variability. Increased knowledge of the multiple phenotypes of C. auris increases the chance of isolating and identifying C. auris by reducing the risk of discarding false negative alternate colony morphologies.

Direct Detection of Emergent Fungal Pathogen Candida auris in Clinical Skin Swabs by SYBR Green-Based Quantitative PCR Assay.

The recent emergence of the multidrug-resistant and pathogenic yeast Candida auris continues to cause public health concern worldwide. C. auris is alarming because it causes health care-associated outbreaks and can establish invasive infections with high mortality rates. Transmission between patients is facilitated by the ability of C. auris to persistently colonize multiple body sites, including the skin, and survive for weeks on surfaces in health care settings. Rapid identification of colonized patients is needed to implement timely infection control measures. Currently, CDC laboratories use an enrichment culture-based approach that can take up to 2 weeks to identify C. auris from composite swabs from the bilateral axillae and groin. A rapid SYBR green quantitative PCR (qPCR) assay that can identify C. auris in a single day was recently described. In this study, we developed the SYBR green qPCR assay further by incorporating a DNA extraction procedure for skin swabs and by including an internal amplification control based on the distinguishable melt curve of a lambda DNA amplicon. The assay was conducted using 103 clinical axilla/groin skin swab samples. Using the enrichment culture-based approach as a gold standard, we determined that the SYBR green C. auris qPCR has a sensitivity of 0.93 and specificity of 0.96. Overall, we found that the SYBR green C. auris qPCR assay can be successfully applied for rapid and accurate detection of C. auris in patient skin swabs, thereby increasing diagnostic options for this emerging pathogen.

Evaluation of a new T2 Magnetic Resonance assay for rapid detection of emergent fungal pathogen Candida auris on clinical skin swab samples.

Candida auris is a multidrug-resistant pathogenic yeast whose recent emergence is of increasing public-health concern. C. auris can colonise multiple body sites, including patients' skin, and survive for weeks in the health care environment, facilitating patient-to-patient transmission and fueling health care-associated outbreaks. Rapid and accurate detection of C. auris colonisation is essential for timely implementation of infection control measures and to prevent transmission. Currently, axilla/groin composite swabs, used to assess colonisation status, are processed using a culture-based method that is sensitive and specific but requires 14 days. This delay limits the opportunity to respond and highlights the need for a faster alternative. The culture-independent T2 Magnetic Resonance (T2MR) system is a rapid diagnostic platform shown to detect target pathogens of interest from unprocessed blood samples in <5 hours. In this study, a new C. auris-specific T2 assay was evaluated for screening of the skin surveillance samples. Inclusivity and limit of detection of the T2 C.  auris assay were assessed with spiked samples in a representative skin flora background. The T2 C. auris assay recognised isolates from each of the 4 known clades of C. auris and consistently detected cells at 5 CFU/mL. Finally, 89 clinical axilla/groin swab samples were processed with the T2 C. auris assay. The culture-based diagnostic assay was used as a gold standard to determine performance statistics including sensitivity (0.89) and specificity (0.98). Overall, the T2 C. auris assay performed well as a rapid diagnostic and could help expedite the detection of C. auris in patient skin swabs.

Survival, Persistence, and Isolation of the Emerging Multidrug-Resistant Pathogenic Yeast Candida auris on a Plastic Health Care Surface.

The emerging multidrug-resistant pathogenic yeast Candida auris represents a serious threat to global health. Unlike most other Candida species, this organism appears to be commonly transmitted within health care facilities and causes health care-associated outbreaks. To better understand the epidemiology of this emerging pathogen, we investigated the ability of C. auris to persist on plastic surfaces common in health care settings compared with that of Candida parapsilosis, a species known to colonize the skin and plastics. Specifically, we compiled comparative and quantitative data essential to understanding the vehicles of spread and the ability of both species to survive and persist on plastic surfaces under controlled conditions (25°C and 57% relative humidity), such as those found in health care settings. When a test suspension of 104 cells was applied and dried on plastic surfaces, C. auris remained viable for at least 14 days and C. parapsilosis for at least 28 days, as measured by CFU. However, survival measured by esterase activity was higher for C. auris than C. parapsilosis throughout the 28-day study. Given the notable length of time Candida species survive and persist outside their host, we developed methods to more effectively culture C. auris from patients and their environment. Using our enrichment protocol, public health laboratories and researchers can now readily isolate C. auris from complex microbial communities (such as patient skin, nasopharynx, and stool) as well as environmental biofilms, in order to better understand and prevent C. auris colonization and transmission.

Evaluation of CHROMagar Candida Plus for the detection of C. auris with a panel of 206 fungal isolates and 83 colonization screening skin-swabs.

CHROMagar Candida Plus is a new formulation of chromogenic media designed for the detection and differentiation of major clinical Candida species, including Candida auris. The objective of this study is to evaluate CHROMagar Candida Plus when used according to manufacturer's instructions with a panel of 206 fungal isolates and 83 skin-swab specimens originally collected for C. auris colonization screening. Of the 68 C. auris isolates tested, 66/68 displayed the expected light-blue colony morphology and blue halo within 48 h. None of the remaining 138 non-auris isolates appeared similar to C. auris. CHROMagarCandida Plus was, therefore, inclusive to 97% of 68 C. auris isolates tested and supported visual exclusion of 100% of the 138 non-C. auris isolates tested. For the 83 colonization screening specimens, direct plating onto CHROMagarCandida Plus was 60% sensitive and 100% specific when compared to the enrichment broth gold-standard reference method. In sum, these findings demonstrate the utility of this media when working with isolates but also notable limitations when working with primary skin-swabs specimens when competing yeast species are present.IMPORTANCECandida auris is an emerging fungal pathogen of public health concern. As it continues to spread, it is important to publish evaluations of new diagnostic tools. In this study, we share our experience with a new chromogenic media which can help distinguish C. auris from related species.

Complete genome sequences of four representative Corynebacterium belfantii strains.

This report describes the complete genome sequence assemblies from four representative isolates of the human pathogen Corynebacterium belfantii. These data provide necessary references to aid accurate sequence-based species discrimination among closely related Corynebacterium spp. pathogens.

Clinical Characteristics, Health Care Utilization, and Outcomes Among Patients in a Pilot Surveillance System for Invasive Mold Disease-Georgia, United States, 2017-2019.

Background: Invasive mold diseases (IMDs) cause severe illness, but public health surveillance data are lacking. We describe data collected from a laboratory-based, pilot IMD surveillance system. Methods: During 2017-2019, the Emerging Infections Program conducted active IMD surveillance at 3 Atlanta-area hospitals. We ascertained potential cases by reviewing histopathology, culture, and Aspergillus galactomannan results and classified patients as having an IMD case (based on European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group [MSG] criteria) or a non-MSG IMD case (based on the treating clinician's diagnosis and use of mold-active antifungal therapy). We described patient features and compared patients with MSG vs non-MSG IMD cases. Results: Among 304 patients with potential IMD, 104 (34.2%) met an IMD case definition (41 MSG, 63 non-MSG). The most common IMD types were invasive aspergillosis (n = 66 [63.5%]), mucormycosis (n = 8 [7.7%]), and fusariosis (n = 4 [3.8%]); the most frequently affected body sites were pulmonary (n = 66 [63.5%]), otorhinolaryngologic (n = 17 [16.3%]), and cutaneous/deep tissue (n = 9 [8.7%]). Forty-five (43.3%) IMD patients received intensive care unit-level care, and 90-day all-cause mortality was 32.7%; these outcomes did not differ significantly between MSG and non-MSG IMD patients. Conclusions: IMD patients had high mortality rates and a variety of clinical presentations. Comprehensive IMD surveillance is needed to assess emerging trends, and strict application of MSG criteria for surveillance might exclude over one-half of clinically significant IMD cases.

Effectiveness of two and three mRNA COVID-19 vaccine doses against Omicron- and Delta-Related outpatient illness among adults, October 2021-February 2022.

Background: We estimated SARS-CoV-2 Delta- and Omicron-specific effectiveness of two and three mRNA COVID-19 vaccine doses in adults against symptomatic illness in US outpatient settings. Methods: Between October 1, 2021, and February 12, 2022, research staff consented and enrolled eligible participants who had fever, cough, or loss of taste or smell and sought outpatient medical care or clinical SARS-CoV-2 testing within 10 days of illness onset. Using the test-negative design, we compared the odds of receiving two or three mRNA COVID-19 vaccine doses among SARS-CoV-2 cases versus controls using logistic regression. Regression models were adjusted for study site, age, onset week, and prior SARS-CoV-2 infection. Vaccine effectiveness (VE) was calculated as (1 - adjusted odds ratio) × 100%. Results: Among 3847 participants included for analysis, 574 (32%) of 1775 tested positive for SARS-CoV-2 during the Delta predominant period and 1006 (56%) of 1794 participants tested positive during the Omicron predominant period. When Delta predominated, VE against symptomatic illness in outpatient settings was 63% (95% CI: 51% to 72%) among mRNA two-dose recipients and 96% (95% CI: 93% to 98%) for three-dose recipients. When Omicron predominated, VE was 21% (95% CI: -6% to 41%) among two-dose recipients and 62% (95% CI: 48% to 72%) among three-dose recipients. Conclusions: In this adult population, three mRNA COVID-19 vaccine doses provided substantial protection against symptomatic illness in outpatient settings when the Omicron variant became the predominant cause of COVID-19 in the United States. These findings support the recommendation for a third mRNA COVID-19 vaccine dose.

Skin Metagenomic Sequence Analysis of Early Candida auris Outbreaks in U.S. Nursing Homes.

Candida auris is a human fungal pathogen classified as an urgent threat to the delivery of health care due to its extensive antimicrobial resistance and the high mortality rates associated with invasive infections. Global outbreaks have occurred in health care facilities, particularly, long-term care hospitals and nursing homes. Skin is the primary site of colonization for C. auris. To accelerate research studies, we developed microbiome sequencing protocols, including amplicon and metagenomic sequencing, directly from patient samples at health care facilities with ongoing C. auris outbreaks. We characterized the skin mycobiome with a database optimized to classify Candida species and C. auris to the clade level. While Malassezia species were the predominant skin-associated fungi, nursing home residents also harbored Candida species, including C. albicans, and C. parapsilosis. Amplicon sequencing was concordant with culturing studies to identify C. auris-colonized patients and provided further resolution that distinct clades of C. auris are colonizing facilities in New York and Illinois. Shotgun metagenomic sequencing from a clinical sample with a high fungal bioburden generated a skin-associated profile of the C. auris genome. Future larger scale clinical studies are warranted to more systematically investigate the effects of commensal microbes and patient risk factors on the colonization and transmission of C. auris. IMPORTANCE Candida auris is a human pathogen of high concern due to its extensive antifungal drug resistance and high mortality rates associated with invasive infections. Candida auris skin colonization and persistence on environmental surfaces make this pathogen difficult to control once it enters a health care facility. Residents in long-term care hospitals and nursing homes are especially vulnerable. In this study, we developed microbiome sequencing protocols directly from surveillance samples, including amplicon and metagenomic sequencing, demonstrating concordance between sequencing results and culturing.

Evaluation of nine surface disinfectants against Candida auris using a quantitative disk carrier method: EPA SOP-MB-35.

We tested 9 disinfectants against Candida auris using the quantitative disk carrier method EPA-MB-35-00: 5 products with hydrogen peroxide or alcohol-based chemistries were effective and 4 quaternary ammonium compound-based products were not. This work supported a FIFRA Section 18 emergency exemption granted by the US Environmental Protection Agency to expand disinfectant guidance for C. auris.